This research will investigate the hormonal dependence of the active fraction of lipoprotein lipase activity in the peripheral tissues. This enzyme is the key enzyme in the catabolism of plasma triglyceride from endogenous or exogenous sources. Recent studies from this laboratory have indicated that only a fraction of total tissue lipoprotein lipase plays a direct role in lipoprotein metabolism and that this fraction is quantitatively identified with the fraction of enzyme released by the rapid perfusion of heparin. This research will investigate the hormonal regulation of the active fraction of lipoprotein lipase. Studies will be made of isolated perfused heart and adipose tissues from fed and fasting animals in the presence and absence of hormones affecting the levels of circulating unesterified fatty acids and the level of intracellular hormone-sensitive lipase. This research will also investigate the peripheral defect of lipolysis in diabetes, and determine the effects of insulin therapy on the ability of tissues from diabetics to catabolize circulating triglyceride. Finally, studies will be made of the effects of ischemia (and of drugs used in the reduction of infarct size) on peripheral lipolysis, particularly in view of the possible role of unesterified fatty acids in potentiating tissue degeneration under these conditions.